For many years glucocorticoids have been used world-wide in pregnant women for treatment of a variety of medical disorders, from bronchial asthma to systemic lupus erythematosous, to renal transplant. More recently their administration has been successfully addressed to the prevention of congenital fetal diseases. In some of these, such as for instance the 21-hydroxylase deficiency leading to congenital adrenal hyperplasia, the pathogenic mechanism is well known, while in others, such as the cystic adenomatoid malformation of the lung, it is not yet understood. Besides these types of diseases, there are acquired inflammatory conditions impairing the physiologic evolution of pregnancy that benefit from glucocorticoid administration. This is the case in recurrent miscarriage due to increased concentration of decidual Natural Killer cells, as well as in the Romero's syndrome, leading to premature parturition and related life threatening fetal complications. However, in spite of its prominent efficacy, the therapy is generally viewed with some suspicion because of possible fetal and maternal adverse effects. With the aim to contribute to a better knowledge of the basic mechanisms of glucocorticoid protection, we reviewed the regulation of their trans-placental passage, their biological effects on gestational environment, their possible 'programming' and teratogenic action, and their accepted use for prevention and cure of pregnancy complications. We believe that a more qualified and liberal use of these compounds will lead in many cases to a significant improvement of fetal and maternal prognosis.